Tumor invasion loci in resected margins of perihilar cholangiocarcinoma and their impact on survival: a retrospective 13-year longitudinal cohort study

Perihilar cholangiocarcinoma (PHC) presents significant challenges in achieving curative resection, with current definitions of radicality (R0/R1/R2) based solely on tumor presence at margins lacking prognostic precision. This study investigates the impact of tumor invasion loci within resection margins on survival and proposes a novel RN0-7 system. A 13-year retrospective cohort study of 83 PHC patients undergoing liver/bile duct resection was conducted. Histopathological evaluation assessed seven invasion loci: bile duct margins, adipose tissue, hepatic parenchyma, vascular/lymphatic structures, perineural spaces, lymph nodes, and radial margins. Margin status was redefined as RN0-7, combining the number of tumor-positive loci (R + 1 to R + 6) with lymph node status (N). Survival analysis utilized Kaplan-Meier and Cox regression methods. Tumor invasion loci were identified in 91.6% of specimens. Multivariate analysis revealed perineural invasion (HR = 14.48, p = 0.03), lymph node involvement (HR = 2.16, p = 0.01), and higher TNM stage (p = 0.006) as key prognostic factors. Survival rates declined progressively with increasing invasion loci: 5-year survival exceeded 60 months for patients with ≤ 2 loci (RN0-2), but dropped significantly with ≥ 3 loci (p < 0.00001). Traditional UICC R0/R1 system poorly correlated with outcomes, as 36.1% classified as R0 exhibited poor survival if multiple loci were involved. RN0-7 system based on the number of tumor invasion loci in resection margins, combined with lymph node status, provides superior prognostic stratification compared to conventional R0/R1 criteria. The invasion loci were selected based on the principle of «assessing tumor infiltration in all anatomical structures within the true resection margin». In our opinion, this approach allowed us to gain a complete understanding (to the best of our ability) of how the “purity” of the resection margin affects survival. This RN0-7 system highlights the importance of quantifying anatomical sites of residual disease, offering a foundation for standardized histopathological evaluation and may have potential significance. This approach may enhance prognostic accuracy and guide therapeutic decisions in PHC, where randomized trials remain impractical.